A recessive form of hyper-IgE syndrome by disruption of ZNF341-dependent STAT3 transcription and activity

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autor(en): Beziat V, Li J, Lin JX, Ma CS, Li P, Bousfiha A, Pellier I, Zoghi S, Baris S, Keles S, Gray P, Du N, Wang Y, Zerbib Y, Levy R, Leclercq T, About F, Lim AI, Rao G, Payne K, Pelham SJ, Avery DT, Deenick EK, Pillay B, Chou J, Guery R, Belkadi A, Guerin A, Migaud M, Rattina V, Ailal F, Benhsaien I, Bouaziz M, Habib T, Chaussabel D, Marr N, El-Benna J, Grimbacher B, Wargon O, Bustamante J, Boisson B, Mueller-Fleckenstein I, Fleckenstein B, Chandesris MO, Titeux M, Fraitag S, Alyanakian MA, Leruez-Ville M, Picard C, Meyts I, Di Santo JP, Hovnanian A, Somer A, Ozen A, Rezaei N, Chatila TA, Abel L, Leonard WJ, Tangye SG, Puel A, Casanova JL
Zeitschrift: Science immunology
Jahr der Veröffentlichung: 2018
Band: 3
Heftnummer: 24
ISSN: 2470-9468


Abstract

Heterozygosity for human signal transducer and activator of transcription 3 (STAT3) dominant-negative (DN) mutations underlies an autosomal dominant form of hyper-immunoglobulin E syndrome (HIES). We describe patients with an autosomal recessive form of HIES due to loss-of-function mutations of a previously uncharacterized gene, ZNF341. ZNF341 is a transcription factor that resides in the nucleus, where it binds a specific DNA motif present in various genes, including the STAT3 promoter. The patients' cells have low basal levels of STAT3 mRNA and protein. The autoinduction of STAT3 production, activation, and function by STAT3-activating cytokines is strongly impaired. Like patients with STAT3 DN mutations, ZNF341-deficient patients lack T helper 17 (T(H)17) cells, have an excess of T(H)2 cells, and have low memory B cells due to the tight dependence of STAT3 activity on ZNF341 in lymphocytes. Their milder extra-hematopoietic manifestations and stronger inflammatory responses reflect the lower ZNF341 dependence of STAT3 activity in other cell types. Human ZNF341 is essential for the STAT3 transcription-dependent autoinduction and sustained activity of STAT3.


FAU-Autoren / FAU-Herausgeber

Fleckenstein, Bernhard Prof. Dr.
Medizinische Fakultät


Autor(en) der externen Einrichtung(en)
Albert-Ludwigs-Universität Freiburg
Boston Children's Hospital
Centre hospitalier universitaire (CHU) d'Angers
Garvan Institute of Medical Research
Hôpital Necker-Enfants malades
Institut Pasteur
Istanbul University / İstanbul Üniversitesi
Marmara University
National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM)
Necmettin Erbakan Üniversitesi
Rockefeller University
Sidra Medical and Research Center
Sydney Children’s Hospitals Network
Tehran University of Medical Sciences
Universität Paris Descartes / Université Paris 5 René Descartes
University Hassan II Casablanca / جامعة الحسن الثانی دارالبیضاء
University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven
University of Paris Diderot / Université Paris Diderot (Paris VII)
US National Institutes of Health (NIH)


Zitierweisen

APA:
Beziat, V., Li, J., Lin, J.-X., Ma, C.S., Li, P., Bousfiha, A.,... Casanova, J.-L. (2018). A recessive form of hyper-IgE syndrome by disruption of ZNF341-dependent STAT3 transcription and activity. Science immunology, 3(24). https://dx.doi.org/10.1126/sciimmunol.aat4956

MLA:
Beziat, Vivien, et al. "A recessive form of hyper-IgE syndrome by disruption of ZNF341-dependent STAT3 transcription and activity." Science immunology 3.24 (2018).

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Zuletzt aktualisiert 2019-04-02 um 14:08